Pulmonary vascular diseases represent an important national health problem. Effective treatment of diseases such as pulmonary hypertension require fundamental knowledge of the structure and function of the pulmonary vascular bed. The purpose of this research program is to improve our knowledge of the physiology, pharmacology and biochemistry of the pulmonary vascular bed. In this program a group of investigators with diverse training will investigate the effects of hypoxia, vasoactive hormones, embolization, endotoxins and other pathologic stimuli on the pulmonary circulation. New techniques will be used to isolate and perfuse the left lower lung lobe in the intact spontaneously breathing dog, cat, monkey, rabbit, sheep, swine and cow. The effects of vasoactive substances will be investigated in normal lungs and when the lung is injured by a variety of pathophysiologic interventions. In these studies the actions of angiotensin I, II and III, bradykinin, prostaglandins, and prostacyclin will be investigated in the normal lung and in the injured lung. The synthesis and metabolism of protaglandins will be investigated in normal lung and in the embolized lung. The effects of adenosine diphosphate will be investigated in normal lung and in injured lung. The effects of inhibitors of prostacyclin synthesis and thromboxane synthesis will be investigated. These studies will improve our fundamental knowledge of the regulation of the pulmonary vascular bed and lead to improved forms of therapy for pulmonary hypertensive and thromboembolic disorders.